TRICuspid-intervention i forsøg med hjertesvigt (TRIC-I-HF)
TRICuspid Intervention in Heart Failure Trial (TRICI-HF-DZHK24)
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
Study design and study aims:
TRIC-I-HF-DZHK24 (TRICuspid Intervention in Heart Failure) is an investigator-initiated, prospective, nationwide, multi-center, randomized, controlled, open label strategy trial in patients with TR and significant right-sided HF. The trial is conducted in 29 German high-volume heart valve centers and will assess whether OMT plus transcatheter tricuspid valve repair in HF patients with severe TR is more effective than OMT alone. TRIC-I-HF-DZHK24 will assess the strategy of TTVI using the individual optimal CE-marked repair device. The optimal TTVI device for the individual patient is determined by the local heart team. TTVI repair devices studied in the trial include devices for T-TEER and transcatheter tricuspid annuloplasty. Patients deemed for tricuspid valve replacement (orthotopic or heterotopic) are excluded from this trial. TRIC-I-HF-DZHK24 will specifically enroll patients with signs of manifest HF to test the impact of TTVI on mortality and HFH in a vulnerable patient cohort with an increased risk for decompensation of HF. Previous randomized-controlled trials enrolled patients without criteria for manifest right-sided HF and observed comparably low event rates for HFH and mortality.
TRIC-I-HF-DZHK24 is funded by the German Center for Cardiovascular Research (DZHK) and co-funded by the university hospital of Ludwig-Maximilians-University, Munich, Germany, and Edwards Lifesciences. An executive steering committee composed of a group of experienced cardiologists in the treatment of HF and TR supports the design and conduct of the study. The industry sponsor is not involved in trial design or conduct and has no direct access to data during the course of the trial. A Data and Safety Monitoring Board will periodically review trial progress and evaluate the accumulated study data for participant safety. An independent Clinical Event Committee will independently adjudicate all hospitalizations. The trial is supported by the Münchner Studienzentrum (MSZ, TUM School of Medicine and Health in Munich) serving as central research organization. The trial is conducted in accordance with Good Clinical Practice, and ethical principles consistent with the Declaration of Helsinki. TRIC-I-HF-DZHK24 has received approval from the responsible local ethics committees prior to inclusion of patients.
Intervention scheme and trial flow:
HF patients with underlying severe TR are screened for eligibility. If all inclusion criteria and none of the exclusion criteria are met and the subject is willing to participate, informed consent for study participation is obtained. Further baseline examination is performed. Randomization will be performed online using pre-defined randomization lists with a 2:1 allocation ratio in favor of the interventional arm. Randomization is stratified by study center and by TR grade. To assure balanced group sizes a block-wise randomization is applied. If a participant is randomized into the control arm, OMT is continued at discharge and follow-up dates are scheduled. In the event of randomization into the interventional arm, TTVI should be scheduled as soon as possible within 14 days after randomization.
Optimal medical therapy: The OMT for the individual patient is defined by the treating physicians and the heart teams of the respective study sites. OMT in patients with chronic right-sided HF includes diuretic therapy titrated to the optimal individual dosage. OMT stability is considered when adequate diuretic therapy at the maximum tolerated dosage is given for at least 30 days. In patients with HFrEF, optimal medical therapy includes guideline-directed medical therapy as recommended by the guidelines for treatment of chronic heart failure.
Transcatheter tricuspid valve intervention: TTVI should be scheduled as early as possible after randomization to the interventional arm to reduce the risk of adverse events before the intervention has been performed. The heart teams decide on the selection of the individual optimal repair device used for TTVI. For study participation, patients need to be treated with CE-marked devices. At the time of study initiation, CE-marked devices for TTVI included T-TEER by PASCAL®, PASCAL ACE® (both Edwards Lifesciences) or TriClip® (Abbott Cardiovascular) as well as direct transcatheter tricuspid annuloplasty by CARDIOBAND® (Edwards Lifesciences). Orthotopic or heterotopic tricuspid valve replacement devices are not studied in this trial. Experience of study sites was set to a minimum of 20 TTVI cases for the desired device before treatment within the trial.
Data Collection:
Baseline evaluation: Diagnostic procedures required for study screening are performed as standard of care. This includes TTE, TEE, right heart catheterization and assessment of the NYHA functional class. If a subject is determined as eligible study candidate and informed consent was obtained, several baseline examinations need to be performed. This baseline evaluation includes information on demographics and past medical history, electrocardiogram (ECG), physical assessment, medication, laboratory results, and assessment of standardized 6-minute walking distance test. QoL is assessed by the standardized Kansas City Cardiomyopathy Questionnaire (KCCQ). In collaboration with the DZHK, a predefined set of biosamples is taken and included into a central biobank, if the subject agrees and specific informed consent was obtained.
Echocardiographic image acquisition and central image analysis: A comprehensive TTE exam is required for screening and should be performed or repeated within one week (maximum of four weeks) before patient enrollment. All TTE images (screening TTE, discharge TTE in the event of randomization to the interventional arm, follow-up TTEs after 1 month, 1 year, 2 years and 3 years) are uploaded to a central image laboratory for further image assessment. Pseudonymization, image transfer, and image quality checks are performed by the respective core facilities at the DZHK (German Center for Cardiovascular Research). Additional TEE imaging is performed during the screening visit to evaluate the anatomy of the tricuspid valve and right heart. This anatomic information is required for clinical decision making and is used to assess eligibility for study participation.
Follow-up assessment: Follow-up evaluations are performed at 1 month (assessing procedural safety) and at 1 year, 2 years, and 3 years (assessing procedural efficacy) after randomization (control arm) or after discharge of TTVI procedure (interventional arm). All follow-up evaluations should be performed on-site and include assessment of the NYHA functional class, TTE, ECG, physical assessment, medication, laboratory results, 6-minute walking distance test, and KCCQ. Events of hospitalization are specifically enquired, if not reported earlier. Adverse events and severe adverse events are documented immediately throughout the course of the study. Follow-up TTEs are sent to the central image laboratory for independent analysis.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Bad Oeynhausen, Tyskland
- Herz- und Diabeteszentrum Nordrhein-Westfalen
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Berlin, Tyskland
- Deutsches Herzzentrum Berlin
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Berlin, Tyskland
- Charité Universitätsmedizin Berlin
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Bernau, Tyskland
- Immanuel Klinikum Bernau Herzzentrum Brandenburg
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Bonn, Tyskland
- Universitatsklinikum Bonn
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Bremen, Tyskland
- Herzzentrum Bremen
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Cologne, Tyskland
- Herzzentrum Uniklinik Köln
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Dortmund, Tyskland
- St.-Johannes-Hospital Dortmund
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Düsseldorf, Tyskland
- Universitätsklinikum Düsseldorf
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Erfurt, Tyskland
- Helios Klinikum Erfurt
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Essen, Tyskland
- Universitätsklinikum Essen
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Frankfurt, Tyskland
- Universitätsklinikum Frankfurt
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Freiburg im Breisgau, Tyskland
- Universitatsklinikum Freiburg
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Hamburg, Tyskland
- Asklepios Klinikum St. Georg
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Hamburg, Tyskland
- Herzzentrum UKE
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Hamburg, Tyskland
- Katholisches Marienkrankenhaus Hamburg
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Heidelberg, Tyskland
- Universitatsklinikum Heidelberg
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Jena, Tyskland
- Universitatsklinikum Jena
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Kiel, Tyskland
- Universitatsklinikum Schleswig-Holstein
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Leipzig, Tyskland
- Herzentrum Leipzig
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Lübeck, Tyskland
- Universitätsklinikum Schlewsig-Holstein Campus Lübeck
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Mainz, Tyskland
- Universitatsmedizin Mainz
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München, Tyskland
- LMU Klinikum
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Siegburg, Tyskland
- Herzzentrum Siegburg
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Stuttgart, Tyskland
- Robert Bosch Klinikum Stuttgart
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Tübingen, Tyskland
- Universitatsklinikum Tubingen
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Ulm, Tyskland
- Universitätsklinikum Ulm
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Wuppertal, Tyskland
- Helios Klinikum Wuppertal
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Beskrivelse
Følgende inklusionskriterier blev defineret for at sikre generaliserbarheden af den population, der skulle undersøges:
- Forsøgspersonen er symptomatisk på grund af svær TR på trods af at have været på stabil OMT i mindst 30 dage baseret på vurdering fra det lokale hjerteteam. Patienter med reduceret venstre ventrikulær ejektionsfraktion (HFrEF) vil sandsynligvis udgøre en minoritet blandt berettigede patienter med isoleret svær tricuspidal regurgitation (9,13). HFrEF-patienter, der er indskrevet i forsøget, skal dog være i stabil retningslinje-styret medicinsk behandling i mindst 4 uger.
- Forsøgspersonen har mellemliggende eller større estimeret risiko for dødelighed med trikuspidalklapkirurgi baseret på vurdering fra det lokale hjerteteam
- New York Heart Association (NYHA) funktionsklasse II, III eller IVa
- Femoral veneadgang og klapanatomi er bestemt til at være mulige for interventionel behandling (herunder tilstrækkelig kvalitet af TTE og TEE billeddannelse)
- Alder ≥ 18 år på tidspunktet for samtykke
- Forsøgspersonen skal give skriftligt informeret samtykke forud for enhver prøverelateret procedure
Følgende eksklusionskriterier blev udvalgt til at definere en repræsentativ undersøgelseskohorte:
- Tilstedeværelse af alvorlig aorta-, mitral- eller pulmonalklapsygdom ELLER kirurgisk/interventionel behandling ved aorta-, mitral- eller lungeklapperne inden 60 dage
- Højre hjertekateterisering (obligatorisk) med systolisk pulmonært arterietryk > 70 mmHg eller væsentlig prækapillær pulmonal hypertension (defineret som gennemsnitligt pulmonalarterietryk (mPAP) >30 mmHg plus transpulmonal gradient (TPG) >17 mmHg eller pulmonal vaskulær modstand (PVR) > 5 træenheder)
- Trikuspidalklapstenose (tricuspid middelgradient > 5 mmHg)
- Pacemaker- eller ICD-ledninger, der ville forhindre passende TTVT
- Tidligere trikuspidalklapprocedurer eller trikuspidalklapbladsanatomi, der ville interferere med passende TTVT (f.eks. forkalkning, Ebstein-anomali, koaptationsdefekt > 8 mm for planlagt folder- og annuloplastik-baseret terapi)
- Kronisk nyresvigt, der kræver dialyse
- Trikuspidalklappens anatomi kan ikke evalueres af TTE og TEE
- Myokardieinfarkt eller cerebrovaskulær ulykke inden for de foregående 90 dage
- Forventet levetid på mindre end 12 måneder
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Enkelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Eksperimentel intervention
Transkateter trikuspidalklapbehandling (TTVT) plus optimal medicinsk terapi (OMT)
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Perkutan CE-mærket godkendte teknikker til transkateter trikuspidalklapbehandling (TTVT): Disse omfatter (I) transkateter annuloplastikanordninger (Tricuspid Cardioband) og (II) transkateter kant-til-kant reparation (TriClip, PASCAL).
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Ingen indgriben: Kontrolindgreb
OMT til svær tricuspid regurgitation ved højresidig hjertesvigt
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Composite of mortality, heart failure hospitalization and quality of life improvement
Tidsramme: 12 months
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Hierarchical composite of all-cause mortality, number of HFH, and lack of QoL improvement (KCCQ improvement of at least 15 points between baseline and follow-up) at 12 months
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12 months
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All-cause mortality or heart failure hospitalization
Tidsramme: minimum follow-up of 12 months
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Composite of time to all-cause mortality or heart failure hospitalization - whichever occurs first - at a minimum follow-up of 12 months
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minimum follow-up of 12 months
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Dødelighed af alle årsager (ujusteret og justeret for TR-sværhedsgrad ved baseline)
Tidsramme: 12 måneder
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12 måneder
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Hjertesvigt indlæggelser (hyppighed og længde; ujusteret og justeret for TR-sværhedsgrad ved baseline)
Tidsramme: 12 måneder
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12 måneder
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Ændring i livskvalitet som vurderet af MLHFQ fra baseline
Tidsramme: 12 måneder
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12 måneder
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Re-interventionsrater for tilbagevendende tricuspid regurgitation
Tidsramme: 12 måneder
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12 måneder
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Ændring i NYHA-klasse fra baseline (≥III/IV til ≤I/II)
Tidsramme: 12 måneder
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12 måneder
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Ændring i 6 minutters gangtestafstand fra baseline
Tidsramme: 12 måneder
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12 måneder
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Ændring i ekkokardiografiske parametre (bl.a.: TR grad I-V, RV dimension og funktion, LV dimension og funktion, estimering af sPAP)
Tidsramme: 12 måneder
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12 måneder
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Udvikling af trikuspidalstenose (gennemsnitlig indstrømningsgradient >5 mmHg)
Tidsramme: 12 måneder
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12 måneder
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Ændring i perifert ødem vurderet ved ødemskalaen (grad I-IV) og forsøgspersonens vægt (kilogram) fra baseline
Tidsramme: 12 måneder
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12 måneder
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Ændring af vanddrivende medicin og hjertesvigtsmedicin fra baseline (type og dosis)
Tidsramme: 12 måneder
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12 måneder
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Ændring i laboratoriemarkører for hjerte-, nyre- og leverfunktion (komplet blodtælling, NT-proBNP, eGFR, serumkreatinin, bilirubin, AST, ALT og gGT)
Tidsramme: 12 måneder
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12 måneder
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Sikkerhed ved indgreb i transkateter trikuspidalklap
Tidsramme: 1 måned
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Større uønskede hændelser, der er relateret til interventionen og er relevante for patienter, der gennemgår TTVT: Mortalitet, livstruende blødning (defineret som BARC-blødning type 3 og 5), større vaskulære eller kardiale strukturelle komplikationer, der kræver intervention, eller mekanisk kredsløbsstøtte.
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1 måned
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Samarbejdspartnere og efterforskere
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- TRIC-I-HF (Anden identifikator: LMU Munich)
- TRICI-HF (Anden identifikator: LMU Munich)
- TRIC-I-HF-DZHK24 (Andet bevillings-/finansieringsnummer: Deutsches Zentrum für Herzkreislaufforschung)
- TRICIHF (Anden identifikator: LMU Munich)
- TRICI HF (Anden identifikator: LMU Munich)
- TRIC-I HF (Anden identifikator: LMU Munich)
Plan for individuelle deltagerdata (IPD)
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